Combining X-rays, neutrons and electrons, and NMR, for precision and accuracy in structure-function studies

Area of Science:

• Structural biology
• Biophysics
• Molecular imaging

Background:

• Physics-based probes are crucial for understanding matter's structure, particularly in biological sciences.
• Modern structural biology faces challenges with reductionism and defining the molecular level.
• Accuracy and precision are key principles, with their boundaries explored in structural studies.

Purpose of the Study:

• To describe physics-based probes for structural biology in a holistic context.
• To explore the interplay of accuracy, precision, and predictive power in structural determination.
• To showcase the application of combined probes for artifact-free structure-function studies.

Main Methods:

• Utilizing a combination of physics-based probes for enhanced accuracy.
• Comparing cryo and room-temperature protein crystal structures.
• Integrating small-angle X-ray scattering (SAXS) in solution and electron microscopy (EM) with crystallography.

Main Results:

• Demonstrated time-resolved X-ray Laue crystallography of enzyme Michaelis complexes.
• Predicted a novel iodoplatin for radiation therapy from platin crystal structure studies.
• Showcased carotenoid color as an assay for protein-bound and unbound function.

Conclusions:

• Complementarity and combinatory use of probes are fundamental for biologically relevant, artifact-free structure-function studies.
• Technological advancements in X-ray, neutron, electron microscopy, and NMR are transforming structural science methodologies.
• Protein structure prediction from gene sequence (e.g., CASP14) is opening new avenues in structural sciences.